For the last several years, our laboratory has been concerned with the biochemistry and genetics of the class I antigens of the major histocompatibility complex of the mouse. We have found that beta-2 microglobulin displays genetic structural polymorphism, which has made it possible to map the B2m locus to the H-3 region of chromosome 2. We have been involved in a long-term program using biochemical techniques to study the genetics of the Qa-Tla region of the MHC. These studies are beginning to provide an understanding of the unusual immunogenetic features of this region, particularly the anomalous expression of Qa and TL antigens on leukemias. We have found that the Tla region genotype (chromosome 17) influences the quantity of B2M (coded by chromosome 2); measurement of B2M messenger RNA levels indicates that this control is exerted at the transcriptional level. We have used molecular biological criteria to detect genetic polymorphism of a novel chromosome 17 gene, an alpha-hemoglobin pseudogene, and demonstrated that it is closely linked to the distal side of the H-2K locus. We intend to continue these studies by carrying out experiments on the biochemical genetics of class I antigens, including molecular-biological techniques, with special emphasis on control of B2m expression by the Tla region, dissection of the complexity of the Qa-Tla region gene products, and analysis of the nature of the expression of the Qa-Tla region gene products on leukemias and normal cells. (LB)